Technetium arcitumomab is a drug used for the diagnostic imaging of colorectal cancer

Colorectal cancer

Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....

s, marketed by Immunomedics. It consists of the Fab' fragment of a monoclonal antibody (arcitumomab, trade name CEA-Scan) and a radionuclide

Radionuclide

A radionuclide is an atom with an unstable nucleus, which is a nucleus characterized by excess energy available to be imparted either to a newly created radiation particle within the nucleus or to an atomic electron. The radionuclide, in this process, undergoes radioactive decay, and emits gamma...

, technetium-99m

Technetium-99m

Technetium-99m is a metastable nuclear isomer of technetium-99, symbolized as 99mTc. The "m" indicates that this is a metastable nuclear isomer, i.e., that its half-life of 6 hours is considerably longer than most nuclear isomers that undergo gamma decay...

.

Chemistry

Technetium (^99mTc) arcitumomab is an immunoconjugate

Immunoconjugate

Immunoconjugates are antibodies conjugated to a second molecule, usually a toxin, radioisotope or label.These conjugates are used in immunotherapy and to develop monoclonal antibody therapy as a targeted form of chemotherapy when they are often known as antibody-drug conjugates.When the conjugates...

. Arcitumomab is a Fab' fragment of IMMU-4, a murine IgG1 monoclonal antibody extracted from the ascites

Ascites

Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...

 of mice. The enzyme pepsin

Pepsin

Pepsin is an enzyme whose precursor form is released by the chief cells in the stomach and that degrades food proteins into peptides. It was discovered in 1836 by Theodor Schwann who also coined its name from the Greek word pepsis, meaning digestion...

 cleaves the F(ab')₂ fragment off the antibody. From this, the Fab' fragment is prepared by mild reduction.

Before application, arcitumomab is reconstituted with a solution of the radioactive agent sodium pertechnetate

Pertechnetate

The pertechnetate ion is an oxoanion with the chemical formula TcO4−. It is often used as a convenient water-soluble source of isotopes of the radioactive element technetium...

 (^99mTc) from a technetium generator.

Mechanism of action

Arcitumomab recognizes carcinoembryonic antigen

Carcinoembryonic antigen

Carcinoembryonic antigen is a glycoprotein involved in cell adhesion. It is normally produced during fetal development, but the production of CEA stops before birth. Therefore, it is not usually present in the blood of healthy adults, although levels are raised in heavy smokers...

 (CEA), an antigen over-expressed in 95% of colorectal cancers. Consequently, the antibody accumulates in such tumours together with the radioisotope, which emits photon

Photon

In physics, a photon is an elementary particle, the quantum of the electromagnetic interaction and the basic unit of light and all other forms of electromagnetic radiation. It is also the force carrier for the electromagnetic force...

s. Via single photon emission computed tomography

Single photon emission computed tomography

Single-photon emission computed tomography is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information...

 (SPECT), high-resolution images showing localisation, remission or progression, and metastases of the tumour can be obtained.

Contraindications

Technetium (^99mTc) arcitumomab is contraindicated for patients with known allergies or hypersensitivity to mouse proteins, as well as during pregnancy. Women should pause breast feeding for 24 hours after application of the drug.

Adverse effects and overdose

Only mild and transient side effects have been observed, mostly immunological reactions like eosinophilia

Eosinophilia

Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...

, itching and fever. Some patients develop human anti-mouse antibodies

Human anti-mouse antibody

Human anti-mouse antibody is an antibody found in humans which reacts in immunoglobins found in mice.-The HAMA response:Antibody treatment is a type of therapy that is used to treat certain types of cancer and immune disorders. Antibodies are proteins which are naturally formed by the body in...

, so there is the theoretical possibility of anaphylactic reactions. High doses of IMMU-4 (up to 20-fold diagnostic arcitumomab dose) have not lead to any serious events. One patient has been reported to develop a grand mal after application.

Radioactivity can lead to radiation poisoning

Radiation poisoning

Acute radiation syndrome also known as radiation poisoning, radiation sickness or radiation toxicity, is a constellation of health effects which occur within several months of exposure to high amounts of ionizing radiation...

. Since the dose of an arcitumomab application is about 10 mSv

Sievert

The sievert is the International System of Units SI derived unit of dose equivalent radiation. It attempts to quantitatively evaluate the biological effects of ionizing radiation as opposed to just the absorbed dose of radiation energy, which is measured in gray...

, such an overdose is unlikely.

Further reading